Pilot Study of Paclitaxel Plus Pembrolizumab in Metastatic HER2-Negative Breast Cancer

NCT03018080 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB0008137000019078LCI-BRE-H2N-PEPP-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to assess the safety and feasibility of the following two regimens: Cohort A) phased regimen of pembrolizumab in which paclitaxel is followed by paclitaxel plus pembrolizumab and Cohort B) concurrent regimen of paclitaxel plus pembrolizumab. The primary safety objective is to evaluate the overall grade 3 or 4 treatment-related adverse event rate for each cohort and compare them to relevant historical controls.

Conditions

Breast - Female; Male Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With at Least One Grade 3 or 4 Treatment-related Adverse Event

  Grade 3 or 4 study treatment-related adverse events will be determined for each subject as a binary variable indicating whether or not the subject experienced at least one grade 3 or 4 study treatment-related adverse events according to the NCI Common Terminology for Adverse Events, version 4.0. An adverse event will be considered study treatment related if it is determined that the event is at least possibly related to either paclitaxel, pembrolizumab, or both.

  From enrollment to at least 30 days following cessation of study treatment. The median time on treatment was 5.5 months.

Secondary Outcomes (5)

• Number of Subjects With an Objective Response (Per RECIST V1.1)

  From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity (subjects were on treatment for a median of 5.5 months)

• Progression-free Survival (PFS) Per RECIST 1.1

  From treatment start date to date of progression/death, or censored as described; assessed for approximately 2 years.

• Overall Survival (OS)

  From date of treatment start to date of death, or censored as described; assessed for approximately 5 years.

• Number of Subjects With Disease Control (Per RECIST V1.1)

  From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity (subjects were on treatment for a median of 5.5 months)

• Duration of Response (DoR)

  From date of response to date of progression/death, or censored as described above; assessed for approximately 2 years.

Study Arms (2)

Arm A (Phased Pembrolizumab Regimen)

EXPERIMENTAL

Paclitaxel will be given as an IV infusion over 60 minutes, on days 1 and 8 every 21 (+/- 3) days during Cycles 1 and 2. No pembrolizumab will be given during Cycles 1 and 2. Starting with cycle 3 and subsequent cycles, pembrolizumab will be given as an IV infusion over 30 minutes before paclitaxel on day 1 every 21 (+/- 3) days.

Drug: Pembrolizumab; Drug: Paclitaxel

Arm B (Concurrent Pembrolizumab Regimen)

EXPERIMENTAL

Pembrolizumab will be given as an IV infusion on day 1 before paclitaxel every 21 (+/- 3) days. Paclitaxel will be given as an IV infusion over 60 minutes, on days 1 and 8 every 21 (+/- 3) days.

Drug: Pembrolizumab; Drug: Paclitaxel

Interventions

Pembrolizumab DRUG

IV (in the vein) on day 1 of a 21 day cycle

Also known as: Keytruda

Arm A (Phased Pembrolizumab Regimen); Arm B (Concurrent Pembrolizumab Regimen)

Paclitaxel DRUG

IV (in the vein) on days 1 and 8 of a 21 day cycle

Also known as: Taxol

Arm A (Phased Pembrolizumab Regimen); Arm B (Concurrent Pembrolizumab Regimen)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following criteria:
• Histologically or cytological confirmed diagnosis of HER2-negative metastatic breast cancer or locally advanced disease not amenable to resection.
• Available ER and PR status from tumor sample with either hormone receptor positive or negative tumor(s).
• For subjects with hormone receptor-positive, HER2-negative metastatic breast cancer, they are eligible if they have already received or been intolerant to at least two lines of endocrine therapies (including the adjuvant and/or metastatic setting), or are appropriate candidates for chemotherapy (i.e. large burden of visceral disease).
• Measurable disease by RECIST 1.1, or evaluable bone disease, i.e., bone lesions that are lytic or mixed (i.e. lytic + sclerotic) in the absence of measurable lesion. Refer to section 11 for the evaluation of measurable disease.
• Male or female age ≥18 years.
• ECOG performance status 0, 1 or 2.
• Must have normal organ and marrow function as defined below:
• Hematologic - Absolute neutrophil count ≥1,500/mcL
• \- Platelets ≥75,000/mcL
• \- Hemoglobin ≥ 9 g/dL
• Renal
• Creatinine ≤ 1.5X ULN or
• Measured or calculated creatinine clearance (CrCl) ≥ 30 mL/min for subject with creatinine levels \> 1.5X ULN \[CrCl should be calculated per institutional standard; GFR can also be used in place of creatinine or CrCl\]
• Hepatic

You may not qualify if:

• Subjects must not meet any of the following criteria:
• Prior chemotherapy within 3 weeks, prior targeted small molecule therapy or radiation therapy within 2 weeks, or prior anti-cancer monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks prior to Cycle 1 Day 1.
• Not recovered (i.e., ≤ Grade 1) from adverse events due to agents previously administered.
• o Note: Subjects with ≤ Grade 2 neuropathy or alopecia of any grade are an exception and may qualify for the study.
• More than three prior lines of chemotherapy for HER2-negative metastatic disease or for locally advanced disease that is not amenable to resection.
• o Note: Non-Chemotherapy regimens do not count as prior lines (ex: hormonals, biologics)
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137) or has participated in Merck MK-3475 trial(s) and received MK-3475 as part of protocol therapy.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Cycle 1 Day 1
• Has had major surgery within 3 weeks prior to Cycle 1 Day 1.
• Has received any other investigational agents within 4 weeks of Cycle 1 Day 1 of study therapy.
• Known active uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
• o Note: Subjects with treated CNS metastases are eligible if they are asymptomatic, have no requirement for steroids, no requirement for anticonvulsants, and stable CNS radiographic study showing no significant vasogenic edema ≥ 4 weeks since completion of radiation and ≥ 2 weeks since discontinuation of steroids.
• History of known allergic reaction to paclitaxel
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment. Pregnant women are excluded from this study because paclitaxel is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with paclitaxel, breastfeeding should be discontinued if the mother is treated with paclitaxel. These potential risks also apply to pembrolizumab being used in this study.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Related Publications (2)

• Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol. 2016 Jul 20;34(21):2460-7. doi: 10.1200/JCO.2015.64.8931. Epub 2016 May 2.

  PMID: 27138582 BACKGROUND

• Tan AR, Chai SJ, Robinson MM, Hellner LB, Gavini N, Sulai N, Turner JD, Atlas J, Graham DL, Induru RR, Kadakia KC, Vallabhanei GD, Heeke AL, Foureau DM, Fisher JG. A pilot study of paclitaxel plus pembrolizumab in patients with metastatic HER2-negative breast cancer (PePPy). Cancer Research. 2022; 82(4_Supplement): P2-14-03

  RESULT

MeSH Terms

Conditions

Breast Neoplasms, Male

Interventions

pembrolizumab; Paclitaxel

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Chair of Biostatistics Department
• Organization: Levine Cancer Institute

james.symanowski@atriumhealth.org

9804422371

Study Officials

• Antoinette Tan, MD

  Atrium Health (formerly Carolinas HealthCare System)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2017
• First Posted: January 11, 2017
• Study Start: June 12, 2017
• Primary Completion: July 29, 2021
• Study Completion: August 5, 2022
• Last Updated: August 4, 2023
• Results First Posted: October 13, 2022

Record last verified: 2023-07

Locations

US (1)